Photosynthetic cellular substances and methods of use thereof

ABSTRACT

Systems and methods for developing and applying photosynthetic cellular substances to a human or animal for medical, therapeutic or cosmetic uses are provided. Photosynthetic cells, such as algal cells, can be used in these substances to provide the ability to continuously generate oxygen when exposed to a light source or other oxygen-generating trigger. The substances can be developed as a standalone liquid, gel or cream, or embedded within a bandage, mesh, scaffold or other structure with a light source to promote oxygen production. The substances can be applied topically for medical, therapeutic or cosmetic treatments, or injected internally for generation of oxygen within one or more parts of the body.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation to U.S. application Ser. No.14/845,063, filed on Sep. 3, 2015, which claims priority to U.S.Provisional Application No. 62/045,523, filed on September 3,2014, U.S.Provisional Application No. 62/045,524, filed on Sep. 3, 2014, U.S.Provisional Application No. 62/045,525, filed on Sep. 3, 2014. U.S.Provisional Application No. 62/045,527, filed on Sep. 3, 2014, U.S.Provisional Application No. 62/045,528, filed on Sep. 3, 2014, U.S.Provisional Application No. 62/045,530 filed on Sep. 3, 2014 and U.S.Provisional Application No. 62/092,229, filed on Dec. 15, 2014, all ofwhich are incorporated by reference in its entirety.

BACKGROUND Field of the Invention

The embodiments described herein are concerned with photosyntheticcellular substances that produce and deliver oxygen to a human or animalfor use in a variety of medical, therapeutic and cosmetic applications.

Related Art

The use of oxygen as a therapeutic or healing agent in the medical fieldis well known but limited in use, primarily due to the difficulty ofdelivering oxygen to a human or animal. The most widely knownapplication of oxygen is in the use of a hyperbaric chamber, which is atightly sealed environment where the atmospheric pressure and oxygenconcentration can be adjusted to higher than atmospheric levels toprovide treatment for wounds and other diseases. However, the expenseand difficult of use of the hyperbaric chamber make it a scarce item inhealth care, limiting its ability for treatment to the vast majority ofpatients that may benefit from it.

Additionally, the hyperbaric chamber primarily increases only theambient oxygen that interacts with the surface of the patient's skin,and does not generally provide increased delivery of oxygen within thebody. It has already been suggested that hypoxia could be partiallyresolved by the use of oxygen carriers. For example T. Henkel-Honke etal. (Reviewed by Henkel-Honke T., Oleg M. Artificial oxygen carriers: Acurrent review. AANA J. 75, 205-211, 2007) mention the incorporation ofoxygen carriers like hemoglobin or perfluorocarbons in scaffolds fortissue engineering. Although these carriers are able to provide oxygenimmediately, they do not provide a constant source of oxygen and, thus,are useful only for a short period of time.

Moreover, in EP 1351623 implantable devices containing living cells in achamber are disclosed for the release of substances out of the chamber.The purpose of such device is to carry and maintain functional cells,wherein the functional cells are cells that express and secrete asubstance that is necessary for an organism in which the device has beenimplanted. The functional cells shall produce substances such as insulinor testosterone which are secreted into the organism. In order tomaintain the functional cells in the device, photosynthetic cells areprovided in a second chamber, separated by a semi-permeable wall thatdelivers oxygen to the functional cells. To maintain the photosyntheticcells that can grow only in the presence of light the cells areilluminated by a light source in the chamber. Thus, the oxygen levelwithin the chamber can be maintained on a predetermined level.

SUMMARY

Embodiments described herein provide for systems and methods fordeveloping and applying photosynthetic cellular substances to a human oranimal for medical, therapeutic or cosmetic uses. Photosynthetic cells,such as algal cells, may be used in these substances to provide theability to continuously generate oxygen when exposed to a light sourceor other oxygen-generating trigger. The substances can be developed as astandalone liquid, gel or cream, or embedded within a bandage, mesh,scaffold, surgical suture or other structure with a light source topromote oxygen production. The substances can be applied topically formedical, therapeutic or cosmetic treatments, or injected internally forgeneration of oxygen within one or more parts of the body.

Other features and advantages of the present invention will become morereadily apparent to those of ordinary skill in the art after reviewingthe following detailed description and accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The structure and operation of the present invention will be understoodfrom a review of the following detailed description and the accompanyingdrawings in which like reference numerals refer to like parts and inwhich:

FIG. 1 illustrates how photosynthetically active cells are seeded into astructure for producing oxygen when exposed to a light source, accordingto an embodiment .

FIG. 2 is a series of images of a light-emitting dressing thatincorporates the structure of FIG. 1 with a light source for applicationon a surface of an animal, according to an embodiment.

FIG. 3 is a series of images of an illumination container holding aphotosynthetic cellular substance with at least one light source in oraround the boundaries of the container to apply light for producingoxygen, according to an embodiment.

FIG. 4 is an image of a photosynthetic cellular substance imbedded intothe structure, according to an embodiment.

FIG. 5 is an image of the presence of photosynthetic cellular structureswithin a zebrafish embryo; and

FIG. 6 is a series of images of the presence of microalgae within azebrafish larvae.

DETAILED DESCRIPTION

Certain embodiments disclosed herein provide systems and methods fordeveloping and applying photosynthetic cellular substances to a human oranimal for medical, therapeutic or cosmetic uses. Photosyntheticstructures, such as algal cells, photosynthetic bacteria, isolatedchloroplasts, cells obtained from vascular plants, etc. can be utilizedin these substances to provide the ability to continuously generateoxygen when exposed to a light source or other oxygen-generatingtrigger. The substances can be developed as a standalone liquid, gel orcream, or embedded within a bandage, mesh, patch, scaffold or otherstructure with a light source to promote oxygen production. Thesubstances can be applied topically for medical, therapeutic or cosmetictreatments, or injected internally for generation of oxygen within oneor more parts of the body. After reading this description it will becomeapparent to one skilled in the art how to implement the embodimentsdescribed in various alternative embodiments and alternativeapplications. Thus, although various embodiments will be describedherein, it is understood that these embodiments are presented by way ofexample only, and not limitation. As such, this detailed description ofvarious alternative embodiments should not be construed to limit thescope or breadth of the claims.

-   I. Oxygen-Generating Topical Substances

In one embodiment, photosynthetic cells are photosynthetically activecells which release oxygen as a byproduct of a reaction with light. Thecells can be of several different types, such as unicellular algae, butare capable of existing alongside tissues such as dermal, bone or nervetissue, and even vascular cells that make up the vascular structure orblood and other cells transported therein.

The cells can be combined with one or more liquids, gels or even solidsubstances to create a topical treatment for application to one or moretissues, such as the skin, which provides the benefit of the creation ofoxygen at the application site. The substances can be medicinal anddesigned for application to a wound or other damaged tissue to promotecellular repair and reduce the risk of infection; or therapeutic for thetreatment of chronic infections or cellular damage; or cosmetic for theimprovement of the health of dermal tissue. For example, a topical creamcan be developed that includes algal cells and is applied to the surfaceof a patient's skin. The topical cream can rely upon exposure to ambientlight to produce oxygen.

Algal cells provide the particular benefit of not being identified asforeign structures by the animal or human immune system, which allowsthem to be presented inside the human body without being attacked. Inone embodiment, the algal cells can be encapsulated to minimize the riskof an allergic or other unnatural reaction by an immune system, wherethe encapsulation material is designed with pores to release oxygen andany other therapeutic materials that may need to be disseminated out.

In one example, the substance may be a topical wound healing ointmentfor applying to a cut or other damaged tissue, reducing scars, etc.,where the ointment includes substances for preventing infections,reducing pain and promoting tissue regeneration. The photosyntheticsubstances will produce oxygen to help promote the healing of the wound.

In another example, the substance may be a chemotherapy treatment forskin cancer which is applied to a cancerous portion of the skin toprovide localized therapy to affected tissue and provide the benefit ofgenerating oxygen to promote the healing of healthy tissue.

In a further example, a photosynthetic substance can be created for usein storing organs or other living tissue structures before they areimplanted into a human or animal in order to keep the organ or livingtissue alive and functioning normally until it can be inserted into thehuman or animal and attached with the existing vascular structure. Theorgans or other living tissue can be placed into a solution of thephotosynthetic substance, coated with the substance, wrapped in acovering or injected with the photosynthetic substance. This substancecan also aid in decreasing ischemia-reperfusion injuries.

Other embodiments of the substance can be in the form of a glue or sprayembedded with the photosynthetic cellular structures that can be used indifferent ways for more consistent application to the surface of atissue or improving the ability of the substance to remain in contactwith the tissue without wearing or washing away.

It is also important to note that the cellular structures can bedesigned to produce additional substances in addition to theirphotosynthetic properties, such as cells that produce collagen. Forexample, genetically-modified photosynthetic cells can be created tocombine one or more additional cellular functions with photosyntheticbenefits. Thus, the cellular structures can serve multiple medical,therapeutic or cosmetic purposes.

-   II. Oxygen-Generating Structures

The use of a photosynthetic cellular substance within a bandage, mesh,scaffold or other structure will allow the production of oxygen at thesurface of the skin or exposed tissue to promote the health of thetissue or promote the healing of a wound or other exposed tissue duringregeneration even if the application site is otherwise covered.Structures such as scaffolds or sutures that are embedded in deep tissuelayers provide for the generation of oxygen where oxygen from theenvironment cannot reach. In one embodiment illustrated in FIG. 1 , amesh is embedded with algal cells and then exposed to a light source,which results in the production of oxygen by the algal cells in themesh. FIG. 4 is an image of the algal-embedded mesh in the form of athin, flexible material, which can easily be applied to the surface ofskin or a wound or used to replace a missing tissue.

In one embodiment, a bandage or other more permanent covering can bedesired to keep the substances in place, protect a wound from exposureto the ambient environment, or otherwise generally protect an exposedtissue from contact. The bandage can include an absorbent material suchas a mesh or pad that can include medication, pain relieving agents orother topical substances, and this absorbent material can also becapable of containing the photosynthetic cellular structures; however,in order to provide maximum generation of oxygen, the bandage caninclude a light source that will ensure that the cells continue toproduce oxygen if the bandage otherwise blocks ambient light.

One embodiment of a light source embedded with a bandage is illustratedin FIG. 2 . The bandage can be incorporated into a larger wearablestructure such as a vest or body suit, depending on how large thesurface area for application needs to be. Additionally, the bandage orother covering can be transparent or translucent to avoid the need for aseparate light source to be embedded within the covering. In a separateembodiment, a wearable light producing device can be used separatelyfrom the bandage, such as for therapeutic skin treatments, facial masks,etc.

In one embodiment, the light source can be micro-LED lights that areconfigured to produce any number of different wavelengths, intensitiesand patterns of light that can be deemed to be specifically effectivefor certain types of treatments. The particular wavelengths of lightapplied can vary widely and be as general as any white light, whichprovides the wavelengths that cause photosynthesis and is generallyconsidered to be in the range of approximately 380 nanometers (nm)-780nm. However, in some embodiments, the wavelengths can be narrowlydefined to stimulate a particular type of cell or produce a particularsubstance. For example, specific wavelengths of approximately 420 nm andapproximately 660 nm can be used to stimulate Chlorophyll A, whilespecific wavelengths of approximately 450 nm and approximately 640 nmcan be used to stimulate Chlorophyll B.

Additionally, the light can be delivered in patterns that are timed tooptimize the amount of oxygen being produced by the cells. In oneembodiment, light may be delivered in approximately 12 hour increments,followed by 12 hours of non-activity. The patterns can also bedetermined by feedback from sensors that determine the amount of oxygenbeing generated, as described below.

In one embodiment, the topical structure can be designed as a mask forapplying to a patient's face, or in the shape of another body part suchas a sock, shirt, underwear, etc. for application to that specific areaof a body.

The structure can also include one or more sensors for detecting variousaspects of the treatment or the condition of the tissue being treated.For example, an oxygen sensor can be embedded within a bandage tomeasure the amount of oxygen being produced by the photosyntheticstructures in order to verify that the treatment is effective or ifadditional substances need to be applied. The sensors can transmitinformation to a computing device such as a portable electronic deviceor smartphone for local or remote monitoring of the patient, where anapplication running on the computing device or smartphone can aid inautomatically monitoring the oxygen levels and determining if additionalsubstances need to be applied. The sensors can also provide informationthat will allow the device to modulate the oxygen tension by, forexample, regulating the intensity or pattern of light being applied overthe photosynthetic structure.

FIG. 3 illustrates a further embodiment, where a container or otherstructure can be devised with a light source that applies light to oneor more areas of the interior area of the container from one or moredifferent directions to maximize the application of light and thegeneration of oxygen within the container. A subject such as an animalcan be coated with the substance or resting in a bath of a substance inorder to maximize the exposure to a larger surface. As indicated above,one embodiment can comprise a container such as a cooler for storing anorgan or other tissue that is being transported to a location forimplanting into a patient for a medical procedure. Thus, the cooler maybe fitted with one or more light sources to illuminate the interiorspace of the cooler, and the cooler can be filled with a liquid, gel orother substance that includes the photosynthetic cells in order toproduce oxygen and help maintain the tissue or organ until it can betransplanted. Additionally, the organ or other tissue can also beperfused with photosynthetic cells to increase the supply of oxygen tothe interior portion of the organ or tissue.

In another embodiment, the photosynthetic cells described herein can beused in bio-printing, for example for three-dimensional (3D) printing oftissues, organs and other biological structures and substances.Bio-printing usually requires the placement of many layers of cells intoa particular structure, and these cells may not be provided withadequate oxygen due to the lack of a vascular system to feed nutrientsand other important materials to the cells. Therefore, the inclusion ofphotosynthetic structures such as algal cells in the cellular “ink” usedfor bioprinting a tissue, organ or other cellular structure can provideoxygen to the other cells throughout the structure.

-   III. Internal Applications

The substances described above can also be configured for injection intothe human or animal body for a variety of potential medical ortherapeutic benefits. In one embodiment, the substances can be combinedwith a chemotherapy treatment to be injected into a tumor to aid in thedestruction of the tumor.

In another embodiment, the substances can be injected directly into theblood stream to improve the ability of the blood to carry oxygen. Algalcells for example can supplement or replace red blood cells and deliveroxygen, for example in a diseased person or animal with a red blood celldeficiency, or for application to a specific area of the body that hastissue damage and would benefit from increased oxygen delivery. Thesubstances can also be injected into the body during other surgicalprocedures to avoid risks for cardiac arrest, ischemia or hemorrhage.

In a further embodiment, photosynthetic cells can be used in conjunctionwith stem cell therapies in order to generate oxygen alongside injectedstem cells to increase the effectiveness of the therapy or treatment.For example, if stem cells are used in a specific area of the body, thestem cell solution or substances can include the photosynthetic cellsdescribed herein, which will provide a greater source of oxygen to thestem cells and increase the effectiveness of any treatment or therapybeing provided.

FIG. 5 is an image of the presence of photosynthetic cellular structureswithin a zebrafish embryo. In this experiment, it was demonstrated thatphotosynthetic cellular structures can exist within a living organism.FIG. 6 is a series of images of the presence of microalgae withinzebrafish larvae, again demonstrating the ability of microalgae to existwithin a living organism and continuously produce oxygen.

In a further embodiment, tissue or an organ can be perfused withphotosynthetic cells ex vivo for testing of drugs or other therapies.For example, a tumor can be perfused with photosynthetic cells and keptex vivo for days to test the efficacy of an anti-cancer drug. In anotherexample, a sample of liver tissue may be perfused with photosyntheticcells and kept ex vivo for days to test hepatotoxicity in vitro.

The above description of the disclosed embodiments is provided to enableany person skilled in the art to make or use the invention. Variousmodifications to these embodiments will be readily apparent to thoseskilled in the art, and the generic principles described herein can beapplied to other embodiments without departing from the spirit or scopeof the invention. Thus, it is to be understood that the description anddrawings presented herein represent a presently preferred embodiment ofthe invention and are therefore representative of the subject matterwhich is broadly contemplated by the present invention. It is furtherunderstood that the scope of the present invention fully encompassesother embodiments that may become obvious to those skilled in the artand that the scope of the present invention is accordingly not limited.

-   IV. Applications for Radiation Therapy

Radiation therapy acts through the generation of reactive oxygen species(ROS) that are toxic for the tumor. Oxygen acts as a radiosensitizerthat forms DNA-damaging free radicals and thus improves theeffectiveness of a given dose of radiation. Additionally, somechemotherapeutic agents rely on oxygen for their toxic effects, such asBleomycin, which acts through the production of reactive oxygen species(ROS).

But one significant drawback of photon radiation therapy is that tumorcells become deficient in oxygen. Some tumors can grow beyond theirblood supply, causing a low-oxygen state known as hypoxia. Due tohypoxia, the pO2 in tumors is very low and big doses of radiation arerequired. Studies show that tumor cells in a hypoxic environment aremore resistant to radiation damage than those in a normal oxygenenvironment. Several different methods of solving the hypoxia problem intumors have been proposed, but none have yet effectively proposed asolution.

Therefore, in one embodiment, the photosynthetic cellular substances areapplied to a tumor during radiation therapy along with light to promotephotosynthesis. Oxygen is produced by the photosynthetic cells, whichthen increases the effectiveness of radiation in destroying the tumor.The idea here is to perfuse the tumor with photosynthetic cells andapply light and radiation therapy at the same time.

As consequence of this local and temporary increase in the oxygentension, radiation becomes more toxic for the tumor. Moreover, withsmaller doses required to obtain the same therapeutic effect, thenegative side effects associated with radiation therapy will also bedecreased.

1. A device, comprising a bandage including an absorbent material andembedded with photosynthetic cellular structures; and a light sourceembedded within the bandage configured to provide a certain intensityand pattern of light to the photosynthetic cellular structures, whereinthe light source is configured to produce wavelengths in the range of380 nm to 780 nm, and wherein the photosynthetic cellular structureswithin the device generate oxygen when exposed to the light.
 2. Thedevice of claim 1, wherein the photosynthetic cellular structuresproduce oxygen to help promote the healing of the wound.
 3. The deviceof claim 1, wherein the device is suitable for use as a chemotherapytreatment for skin cancer.
 4. The device of claim 1, wherein the deviceis suitable for use in keeping living tissue alive during storage andbefore implantation.
 5. The device of claim 1, wherein the device issuitable for use during radiation therapy to increase the effectivenessof radiation in destroying a tumor.
 6. The device of claim 1, whereinthe light source is configured to deliver light in a pattern where thelight is alternatingly on for a first period, then off for a secondperiod.
 7. The device of claim 1, wherein the absorbent material is amesh or pad.
 8. The device of claim 1, wherein the photosyntheticcellular structures comprise at least one of algal cells, photosyntheticbacteria, and isolated chloroplasts.
 9. An composition comprisingphotosynthetic cellular structures for perfusing at least one of anorgan and a tissue, wherein the photosynthetic cellular structure, uponperfusing the at least one of the organ and the tissue and exposure tolight, generate oxygen.
 10. The composition of claim 9, whereinperfusing the at least one of the organ and the tissue comprisesperfusing the at least one of the organ and the tissue ex vivo.
 11. Acontainer for preservation of at least one of a tissue and an organ,comprising: one or more light sources configured to illuminate aninterior space of the container; and wherein the one or more lightsources are configured to produce light having wavelengths in the rangeof 380 nm to 780 nm.
 12. The container of claim 11, wherein thecontainer further comprises: a substance including photosyntheticcellular structures; and wherein the container is sized and dimensionedto contain the at least one of the tissue and the organ, and wherein thephotosynthetic cellular structures, upon exposure to the light, generateoxygen that helps maintain the at least one of the tissue and the organfor transplanting.
 13. The container of claim 12, wherein the at leastone of the tissue and the organ is perfused with the substance includingphotosynthetic cellular structures.